HMGCL_BOVIN
ID HMGCL_BOVIN Reviewed; 325 AA.
AC Q29448; Q148J2;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Hydroxymethylglutaryl-CoA lyase, mitochondrial;
DE Short=HL;
DE Short=HMG-CoA lyase;
DE EC=4.1.3.4 {ECO:0000250|UniProtKB:P35914};
DE AltName: Full=3-hydroxy-3-methylglutarate-CoA lyase;
DE Flags: Precursor;
GN Name=HMGCL;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Brain cortex;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 186-325.
RA Ji S., Kuske J., Spurlock M.E.;
RL Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase that
CC catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-
CC methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in
CC ketogenesis. Terminal step in leucine catabolism. Ketone bodies (beta-
CC hydroxybutyrate, acetoacetate and acetone) are essential as an
CC alternative source of energy to glucose, as lipid precursors and as
CC regulators of metabolism. {ECO:0000250|UniProtKB:P35914}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxy-3-methylglutaryl-CoA = acetoacetate + acetyl-CoA;
CC Xref=Rhea:RHEA:24404, ChEBI:CHEBI:13705, ChEBI:CHEBI:43074,
CC ChEBI:CHEBI:57288; EC=4.1.3.4;
CC Evidence={ECO:0000250|UniProtKB:P35914};
CC -!- PATHWAY: Metabolic intermediate metabolism; (S)-3-hydroxy-3-
CC methylglutaryl-CoA degradation; acetoacetate from (S)-3-hydroxy-3-
CC methylglutaryl-CoA: step 1/1.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Can also form homotetramers.
CC {ECO:0000250|UniProtKB:P35914}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P38060}. Peroxisome
CC {ECO:0000250|UniProtKB:P38060}. Note=Unprocessed form is peroxisomal.
CC {ECO:0000250|UniProtKB:P38060}.
CC -!- SIMILARITY: Belongs to the HMG-CoA lyase family. {ECO:0000305}.
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DR EMBL; BC118276; AAI18277.1; -; mRNA.
DR EMBL; U41409; AAA86757.1; -; mRNA.
DR RefSeq; NP_001068600.1; NM_001075132.1.
DR AlphaFoldDB; Q29448; -.
DR SMR; Q29448; -.
DR STRING; 9913.ENSBTAP00000029103; -.
DR PaxDb; Q29448; -.
DR PeptideAtlas; Q29448; -.
DR Ensembl; ENSBTAT00000029103; ENSBTAP00000029103; ENSBTAG00000021832.
DR GeneID; 317658; -.
DR KEGG; bta:317658; -.
DR CTD; 3155; -.
DR VEuPathDB; HostDB:ENSBTAG00000021832; -.
DR VGNC; VGNC:29877; HMGCL.
DR eggNOG; KOG2368; Eukaryota.
DR GeneTree; ENSGT00940000158484; -.
DR HOGENOM; CLU_022138_3_2_1; -.
DR InParanoid; Q29448; -.
DR OMA; FGGCPMA; -.
DR OrthoDB; 1029775at2759; -.
DR TreeFam; TF105363; -.
DR UniPathway; UPA00896; UER00863.
DR Proteomes; UP000009136; Chromosome 2.
DR Bgee; ENSBTAG00000021832; Expressed in digestive system secreted substance and 105 other tissues.
DR ExpressionAtlas; Q29448; baseline and differential.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005777; C:peroxisome; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0004419; F:hydroxymethylglutaryl-CoA lyase activity; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IEA:Ensembl.
DR GO; GO:0030145; F:manganese ion binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; ISS:UniProtKB.
DR GO; GO:0005198; F:structural molecule activity; IEA:Ensembl.
DR GO; GO:0046951; P:ketone body biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006552; P:leucine catabolic process; IBA:GO_Central.
DR GO; GO:0006629; P:lipid metabolic process; IBA:GO_Central.
DR GO; GO:0007005; P:mitochondrion organization; IEA:Ensembl.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR000138; HMG_CoA_lyase_AS.
DR InterPro; IPR043594; HMGL.
DR InterPro; IPR000891; PYR_CT.
DR PANTHER; PTHR42738; PTHR42738; 1.
DR Pfam; PF00682; HMGL-like; 1.
DR PROSITE; PS01062; HMG_COA_LYASE; 1.
DR PROSITE; PS50991; PYR_CT; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Disulfide bond; Lipid metabolism; Lyase; Metal-binding;
KW Mitochondrion; Peroxisome; Reference proteome; Transit peptide.
FT TRANSIT 1..27
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 28..325
FT /note="Hydroxymethylglutaryl-CoA lyase, mitochondrial"
FT /id="PRO_0000151519"
FT DOMAIN 33..300
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT MOTIF 323..325
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 266
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10115"
FT BINDING 41
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 42
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 233
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 235
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 275
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT MOD_RES 48
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35914"
FT MOD_RES 48
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38060"
FT MOD_RES 111
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P38060"
FT MOD_RES 137
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38060"
FT MOD_RES 137
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38060"
FT MOD_RES 179
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38060"
FT MOD_RES 179
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38060"
FT MOD_RES 324
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P38060"
FT DISULFID 323
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT CONFLICT 221
FT /note="V -> A (in Ref. 2; AAA86757)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 325 AA; 34168 MW; 4EBB2B79B5547564 CRC64;
MATVKKVLPR RLVGLATLRA VSTSSVGTFP KQVKIVEVGP RDGLQNEKNI VPTPVKIKLI
DMLSEAGLPV VEATSFVSPK WVPQMADHAE VLKGIQKFPG VNYPVLTPNF KGFQAAVAAG
AKEVAIFGAA SELFTKKNIN CSIDESLQRF DEILKAARAA GISVRGYVSC VLGCPYEGKI
SPAKVAEVTK KLYSMGCYEI SLGDTIGVGT PGAMKDMLSA VLQEVPVTAL AVHCHDTYGQ
ALANTLTALQ MGVSVMDSSV AGLGGCPYAQ GASGNLATED LVYMLAGLGI HTGVNLQKLL
EAGAFICQAL NRRTNSKVAQ ATCKL
